PXD044958-1

PXD044958 is an original dataset announced via ProteomeXchange.

Title	MALDI imaging and LC-MS/MS-based fast, high-resolution spatial proteomics demonstrate cellular heterogeneity in situ
Description	Highly specialized cells are fundamental for proper functioning of complex organs. Variations in cell-type specific gene expression and protein composition have been linked to a variety of diseases. Although single cell technologies have emerged as valuable tools to address this cellular heterogeneity, a majority of these workflows lack sufficient in situ resolution for functional classification of cells and are associated with extremely long analysis time, especially when it comes to in situ proteomics. In addition, lack of understanding of single cell dynamics within their native environment limits our ability to explore the altered physiology in disease development. This limitation is particularly relevant in the mammalian brain, where different cell types perform unique functions and exhibit varying sensitivities to insults. The hippocampus, a brain region crucial for learning and memory, is of particular interest due to its obvious involvement in various neurological disorders. Here, we present a combination of experimental and data integration approaches for investigation of cellular heterogeneity and functional disposition within the mouse brain hippocampus using MALDI Imaging mass spectrometry (MALDI-IMS) and shotgun proteomics (LC-MS/MS) coupled with laser-capture microdissection (LCM) along with spatial transcriptomics. Within the dentate gyrus granule cells we identified two proteomically distinct cellular subpopulations that are characterized by a substantial number of discriminative proteins. These cellular clusters contribute to the overall functionality of the dentate gyrus by regulating redox homeostasis, mitochondrial organization, RNA processing, and microtubule organization. Importantly, most of the identified proteins matched their transcripts, verifying the in situ protein identification and supporting their functional analyses. By combining high-throughput spatial proteomics with transcriptomics, our approach enables reliable near-single-cell scale identification of proteins and profiling of inter-cellular heterogeneity within similar cell-types in tissues. This methodology has the potential to be applied to different biological conditions and tissues, providing a deeper understanding of cellular subpopulations in situ.
HostingRepository	PRIDE
AnnounceDate	2024-10-17
AnnouncementXML	Submission_2024-10-17_03:21:06.648.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shibojyoti Lahiri
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monomethylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF; rapifleX

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-30 04:47:47	ID requested
⏵ 1	2024-10-17 03:21:07	announced

10.1016/j.mcpro.2024.100811;

Sch, ä, fer F, Tomar A, Sato S, Teperino R, Imhof A, Lahiri S, Enhanced In Situ Spatial Proteomics by Effective Combination of MALDI Imaging and LC-MS/MS. Mol Cell Proteomics, 23(8):100811(2024) [pubmed]

submitter keyword: Cellular heterogeneity, Laser capture microdissection,Imaging mass spectrometry, Proteomics, Data integration, Dentate gyrus

Axel Imhof
contact affiliation	Histone Modifications Group Zentrallabor für Proteinanalytik BioMedical Center Faculty of Medicine Ludwig-Maximilians-University of Munich Großhadernerstr. 9 82152 Planegg-Martinsried GERMANY
contact email	imhof@lmu.de
lab head
Shibojyoti Lahiri
contact affiliation	Ludwig-Maximilians-University of Munich
contact email	shibojyoti.lahiri@med.uni-muenchen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044958
     1. Label: PRIDE project
     2. Name: MALDI imaging and LC-MS/MS-based fast, high-resolution spatial proteomics demonstrate cellular heterogeneity in situ